Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma

Leung, Wai Keung; To, Ka Fai; Go, Minnie Y.Y.; Chan, Ka‐Kui; Chan, Francis K.L.; Ng, Enders K.W.; Chung, S. C.Sydney; Sung, Joseph J.Y.

doi:10.3892/ijo.23.5.1317

Cited by 61 publications

(51 citation statements)

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“…VEGF is one of the most potent angiogenic factors and is crucial for the persistent proliferation and metastasis of tumor cells (9). The expression of VEGF and COX-2 is closely associated with clinical stage, lymph node metastasis and prognosis of gastric cancer, suggesting that these factors play important roles in the development of gastric cancer (10).…”

Section: Introductionmentioning

confidence: 99%

Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer

Han¹,

Li²,

Su³

et al. 2013

Biomedical Reports

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Section: Introductionmentioning

confidence: 99%

Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer

Han¹,

Li²,

Su³

et al. 2013

Biomedical Reports

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“…8,[12][13][14][15][16][17] Inhibition of angiogenesis also plays a role in the chemoprevention of COX-inhibitors. Expression of COX-2 is found to be associated with VEGF expression and microvessel density (MVD) in gastric cancer, [18][19][20][21] and NSAIDs were found to inhibit in vitro angiogenesis of human microvascular endothelial cells. 22,23 In addition, inhibition of extracellular adhesion molecule such as E-cadherin has also been linked to the chemoprevention effect of COX-2 inhibitors.…”

Section: Introductionmentioning

confidence: 99%

Effect of celecoxib on E-cadherin, VEGF, microvessel density and apoptosis in gastric cancer

Zhou¹,

Ran²,

Tang³

et al. 2007

Cancer Biology & Therapy

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Cyclooxygenase-2 (COX-2) plays a crucial role in the development and invasion of gastric cancer. COX-2 inhibitors have been shown to be chemopreventive against gastrointestinal cancers. In vitro studies have suggested that the mechanisms may be related to induction of apoptosis and inhibition of angiogenesis. COX-2 may also have impact on E-cadherin. In our study we investigate the effect of Celecoxib on expression of E-cadherin and serum soluble E-cadherin, as well as on apoptosis and angiogenesis in patients with gastric cancer. Fifty nine gastric cancer patients were randomly divided into two groups: Surgery group (n = 22), in which patients underwent surgical resection after diagnosis, and Celecoxib + Surgery group (n = 37), in which patients received oral Celecoxib 200 mg twice daily for 7 days before curative resection. Twenty healthy subjects (Healthy controls) were recruited as normal controls. After curative resection, COX-2, E-cadherin, VEGF, and MVD were detected by immunohistochemistry. Serum soluble E-cadherin was quantitatively measured using a commercially available enzyme-linked immunosorbent assay kit. Apoptosis was determined by TUNEL assay. Significantly decreased expression of COX-2, increased E-cadherin and apoptosis, decreased VEGF and MVD were observed in gastric cancer tissues from patients receiving Celecoxib compared to Surgery group. Compared to Healthy controls, the serum soluble E-cadherin levels were higher in gastric cancer patients which were decreased by Celecoxib. This in vivo study demonstrated that Celecoxib induces apoptosis and inhibit angiogenesis of gastric cancer. Its impact on E-cadherin may suggest that this agent may suppress the invasion of advanced gastric cancer.

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“…Li et al [29] reported that COX-2 expression in gastric adenocarcinoma was higher than that in the paracancerous tissues, and was related to lymph node metastasis and the depth of invasion, suggesting COX-2 might be correlated to the occurrence and advancement of gastric carcinoma. Leung et al [30] reported that overexpression of COX-2 in gastric cancer is associated with up-regulation in VEGF and angiogenesis. However, in this study, we observed the expression of COX-1 and COX-2 in both cell lines on Western blotting.…”

Section: Discussionmentioning

confidence: 99%

Comparison between the Gastric Cancer Cell Line MKN-45 and the High-Potential Peritoneal Dissemination Gastric Cancer Cell Line MKN-45P

et al. 2011

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Summary: Peritoneal metastasis is the most common form of recurrence in gastric cancer, and is associated with a poor prognosis. It is clear that many agents are involved at the various stages of this process, however, many aspects of the progression remain unclear. In the present study we compared the gastric cancer cell line MKN-45 with the high-potential peritoneal dissemination gastric cancer cell line MKN-45P, established from MKN-45. The supernatant of culture medium of MKN-45 cells or MKN-45P cells was collected, and the concentrations of interleukin-1β (IL-1β), IL-6, IL-8, hepatocyte growth factor (HGF), Transforming growth factor beta-β1 (TGF-β1), vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 (MMP-2), MMP-9, and tissue inhibitor of metalloproteinase-1 (TIMP-1) proteins were measured using an enzyme-linked immuno sorbent assay (ELISA) method. Invasion, wound healing and adhesion assays were performed in vitro to examine interstitial invasion, migration and adhesion in the gastric cancer cell lines. Moreover, Western blotting was performed to determine the expression of cyclooxygenase-1 (COX-1) and COX-2 proteins in the culture media of the cell lines. The concentrations of IL-6, IL-8, VEGF and MMP-2 protein in the culture supernatant of MKN-45P were significantly higher than those of MKN-45. Percent adhesion of MKN-45P was significantly higher than that of MKN-45 in the fibronectin-coated group. There was no significant difference in invasion or migration between MKN-45 and MKN-45P. COX-1 and COX-2 proteins were observed in both cell lines. These results suggested that secretion of IL-6, IL-8, VEGF and MMP-2 from cancer cells, and adhesion of cancer cells to fibronectin, were related to the establishment of peritoneal dissemination.

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Cyclooxygenase-2 upregulates vascular endothelial growth factor expression and angiogenesis in human gastric carcinoma

Cited by 61 publications

References 0 publications

Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer

Effect of celecoxib plus standard chemotherapy on serum levels of vascular endothelial growth factor and cyclooxygenase-2 in patients with gastric cancer

Effect of celecoxib on E-cadherin, VEGF, microvessel density and apoptosis in gastric cancer

Comparison between the Gastric Cancer Cell Line MKN-45 and the High-Potential Peritoneal Dissemination Gastric Cancer Cell Line MKN-45P

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